The purpose of this study is to determine whether simvastatin is effective in the prevention of progression of porta hypertension in compensated cirrhosis patients.

Decompensation of cirrhosis is associated with a dramatic reduction of survival. Progression of portal hypertension (PHT) is the main determinant of decompensation that appears when portal pressure gradient (PPG) is ≥10mmHg (clinically significant HTP). 40% of compensated cirrhotic patients have mild PHT. However, with progression of disease 41% develop clinically significant PHT. In cirrhosis, PHT results from increased resistance to blood flow, with a dynamic component due to decreased nitric oxide (NO) bioavailability. In advanced disease increased portal venous inflow also contributes to PHT. Beta-blockers have not been useful in compensated cirrhosis with mild PHT. In early cirrhosis, vasodilators may be more adequate. Statins, drugs that inhibit the activity of HMG-CoA reductase, induce selective hepatic vasodilation due to an enhanced bioavailability of NO. Acutely, they decreases hepatic resistance, while with long-term use statins decreases PPG without deleterious effects on systemic circulation. This multicenter, randomized, double-blind placebo-controlled study is aimed at assessing whether treatment with simvastatin may prevent progression of mild PHT (with PPG between 6 and 10 mmHg) to clinically significant PHT. Patients with compensated cirrhosis, without previous decompensation, without esophageal varices at risk and with PPG between 6 and 10 mmHg will be included. The calculated sample size is 80 patients and the duration of the study 4 years (2 years including and a follow-up of at least 2 year).

Inclusion Criteria:

• Liver cirrhosis diagnosed by previous biopsy or by clinical, laboratory, ultrasound
• Portal hypertension gradient between6 mmHg and10 mmHg
• Absence of esophageal and gastric varices or small esophageal varices without red signs
• Absence previous episodes of gastrointestinal hemorrhage, ascites, encephalopathy or jaundice
• Written informed consent

Exclusion Criteria:

• Age <18 and> 80 years,
• Presence or history of ascites, clinical or ultrasound,
• Previous decompensation of liver cirrhosis, ascites or SBP, bleeding varices, large varices, hepatic encephalopathy, jaundice,
• Thrombosis splenoportal,
• Hepatocellular carcinoma;
• Child-Pugh >7 point
• Any comorbidity that leads to a restriction therapy and / or a life expectancy <12 months
• Absolute contraindication to treatment with statins or allergy Simvastatin;
• Concomitant potent CYP3A4 inhibitors (eg., itraconazole, ketoconazole, protease inhibitors, HIV, erythromycin, clarithromycin, telithromycin and nefazodone),
• Pretreatment (<1 month) with simvastatin or other lipid-lowering,
• Previous episodes of rhabdomyolysis,
• Active alcoholic hepatitis,
• Refusal to participate in the study or the informed consent claim;
• Pre-treatment with beta blockers or nitrates, or endoscopic treatment for varicose veins or portosystemic derivations;
• Pregnancy and lactation.